We are examining the mechanisms by which hallucinogenic drugs produce changes in associative processes (i.e., learning) as measured by rates of acquisition of classically conditioned responses in the rabbit. Using the classically conditioned, nictitating membrane response (NMR) we have found that LSD at dosages of 1 to 100 nmol/kg produces a dose-dependent enhancement in the acquisition of conditioned responses (CRs) to both auditory and visual stimuli with peak enhancement occurring at 30 nmol/kg. 300 nmol/kg LSD produces a retardation of acquisition. Separate experiments indicated that these changes in rate of acquisition were not due to: sensitization; pseudoconditioning; changes in baseline level of responding; or changes in threshold of the unconditioned stimulus (paraorbital shock) as might be reflected by frequency or amplitude of NMRs at varying shock intensities. (Therefore, these results suggest that LSD uniquely affects associative processes (learning).) The enhancement of acquisition of the NMR produced by LSD was found to be due, at least in part, to an enhancement of excitability produced by conditioned stimuli (CSs). Thus, experiments in which animals had achieved asymptotic levels of CRs to a 90 db tone and were then exposed to tone intensities varying between 0 to 90 db revealed that LSD produces greater levels of CRs at lower tone intensities as compared with vehicle injected controls. A more direct assessment of CS excitability was obtained by presenting experimentally naive rabbits with a tone followed at various intervals by the paraorbital shock, unconditioned stimulus (UCS). In this situation, the excitability produced by the tone in the unconditioned reflex is seen as an increase in the amplitude of the unconditioned NMR. LSD produced a three-fold increase in excitability as measured in this manner and prolonged the temporal course of the excitation. Similar effects have been obtained using classically conditioned jaw-movement response (JMR) indicating that these effects of LSD are produced in both aversive (NMR) and appetitive (JMR) conditioning.